Rhinovirus (RV) respiratory infections are major causes of acute wheezing in asthma patients. The overall objectives of this application are to establish the mechanisms of the immune response to RV and to determine how this reaction can promote wheezing in patients with asthma. Previous studies have shown that experimental rhinovirus infections enhance both airway responsiveness and the probability of a late allergic reaction to antigen. These observations suggest that viral respiratory illnesses promote asthma by increasing bronchial inflammation. From these findings and new in vitro observations, the investigators hypothesize that rhinovirus-induced production of cytokines augments existing airway inflammation and, thus, leads to persistent lower airway dysfunction in allergic, but not normal subjects. It is proposed that an initial and key step in this process is RV-induced activation of airway macrophage via intercellular adhesion molecule-1 (ICAM-1) receptors. Cytokines produced by activated macrophages, and lymphocytes, can then initiate a series of interrelated cellular processes which increase ICAM-1 on bronchial epithelium, prime eosinophil inflammatory capabilities, and increase eosinophil mediated damage to the airway. To establish, at the cellular and molecular level, how the immune response to RV can induce asthma, isolated human cells will be used for study and compare these findings to ex vivo observations. First, RV-induced production of cytokines (IL-1-beta, TNF-gamma, and GM-CSF) by monocytes/macrophages will be determined by ELISA and a semi-quantitative mRNA assay. RV16, a strain which interacts with ICAM-1 will be used to initiate this response. Next, the contribution of ICAM-1 activation to monocyte/macrophage secretion of cytokines will be determined by the use of anti-ICAM-1 monoclonal antibodies and non-ICAM-1 dependent RV (strain 49); furthermore, the contribution of cell infection by RV will be evaluated by specific RV RNA probes, intercellular virus replication, and ultrastructural morphology. In addition, the subsequent activation of lymphocytes, and generation of cytokines, by either RV-activated monocytes, cytokine generation, or virus itself will be established. Of particular interest will be a comparison of the cytokine profile produced by lymphocytes (Th1 versus Th2), and change in immune function following RV encounter. Finally, the effects of RV activation of monocytes/macrophages and/or lymphocytes will be determined on eosinophil effector function including secretion of inflammatory mediators, interaction with a bronchial epithelial cell line, and damage to the airway tissue.